As the foundation for developing strategies for gene and immunotherapy of neoplasms affecting human communication, research has focused on the identification of immune recognition determinants, components of the inflammatory response, and cytokines in the environment of developing squamous cell neoplasms of the upper aerodigestive tract. Immune and in situ reverse transcription-polymerase chain reaction (RT-PCR) histochemistry are being used to define the cell types present in the tumor environment and expression of gene products involved in immunity. Gene transfer of selected cytokines and recognition determinants which may promote protective helper and cytolytic T lymphocyte immunity to squamous cell carcinoma are being tested in experimental tumor models.